In a surprise move, the House of Lords decided that controversial stem cell research, involving the cloning of human embryos, can now be allowed in the UK. How was this ruling reached? What is the story behind cloning?

The idea of cloning animals was first suggested in 1938 by a German embryologist called Hans Spemann. He proposed what he called a "fantastical experiment" to remove the nucleus from an egg cell and replace it with a nucleus from another cell.

14 years later in 1952, two American scientists, Robert Briggs and Thomas King attempted this. They used very fine pipettes to suck the nucleus from a frog egg and transfer a nucleus sucked from a body cell of an adult frog into its place. The experiment failed when conducted in this way. However, partial success was achieved in 1970 when British developmental biologist, John Gurdon, inserted nuclei from advanced frog embryos rather than adult tissue. The frog eggs developed into tadpoles, but died before becoming adults.

In 1980, the U.S. Supreme Court ruled that live, human-made micro-organisms were patentable material, paving the way to make cloning research profitable. Technology continued to advance and in 1984 Steen Willadsen, a Danish embryologist working in Texas, succeeded in cloning a sheep using a nucleus from a cell of an early embryo. This exciting result was soon replicated by others in a host of other organisms, but it only seemed to work when early embryo cells were used. Researchers began to think that animal embryo cells became irreversibly "committed" after the first few cell divisions and that nuclei from differentiated animal cells could not be used to clone entire organisms.

However, as knowledge of the cell cycle advanced, it became apparent that cells don't divide until conditions are appropriate. Keith Campbell, a geneticist in Scotland reasoned that the egg and the donated nucleus might need to be at the same stage in the cell cycle. In 1995 he and reproductive biologist, Ian Wilmut, succeeded in cloning farm animals from advanced embryos. They then went on to clone an adult mammal for the first time, producing a lamb named "Dolly" from a six-year-old ewe, using tissue taken from the ewe’s udder. She was the only one of 277 nuclear transfers to make it into the world.

In 1997, Wilmut and Campbell created Polly, the first sheep with a human gene in every cell of its body, meanwhile President Bill Clinton banned the use of federal funds for cloning research for five years. Since then scientists have successfully cloned a host of animals, including mice, cattle, goats, and pigs.

Fears of reproductive cloning in the future were raised in 1998 when Richard Seed, a Chicago scientist, announced that he would attempt human cloning in the future. Also in 1998, Bonnie, a natural offspring of Dolly, was born, proving that Dolly is able to breed normally and produce a healthy baby. Britain later went on to issue a patent to Geron Corp. for the cloning process that created Dolly.

In 2001, Britain's House of Lords effectively legalised the creation of cloned human embryos for stem cell research purposes, with the prerequisite that the cloned embryos are destroyed within 14 days. Later in 2001, a Massachusetts research company, Advanced Cloning Technology (ACT), reported that it had cloned the first human embryo, a development it said was aimed at producing genetically matched replacement cells for patients with a wide range of diseases. The success of this was limited, however, while only one of the embryos reached the six-cell stage, all of the company's cloned embryos stopped developing after only a few hours.

The most recent development in the cloning story happened on 27th February 2002 with the House of Lords’ announcement that stem cell research is now legal. This is for therapeutic cloning only, so reproductive cloning is still banned. However, this move still brings fears that it could be the start of a 'slippery slope' towards reproductive cloning with identical copies of human beings, being created.

Update: Since this page was first published, Dolly has been put down. She developed arthritis at the age of five; at six, she was found to have a progressive lung disease usually found in much older sheep and it was decided to bring her famous life to a peaceful close.

Human cloning is one of the most controversial areas of current scientific research. What is the scientific fact behind the hype? This section explains what cloning is and the scientific process behind it.

What is Cloning?
The word cloning simply refers to making identical copies of something from one unit. Although the word may conjure up images of mad scientists making copies of humans, the reality of it is that cloning is currently only being used for medical benefits, and very few scientists have expressed the desire to clone humans. There are three main types of cloning that scientists use: embryo cloning, reproductive cloning and therapeutic cloning. These methods will be explained in more detail later, but firstly, how is cloning achieved?

The Scientific Process of Cloning
Cloning effectively involves turning a normal cell from the body of an animal, back into an embryo. In order to do this, scientists take an egg from the animal that they want to clone, because it will contain the right environment from which an embryo will develop. They then remove the nucleus from the egg, because it contains the DNA. So they then have an empty egg. Next, they take a cell from somewhere else in the animal's body, for example the skin, take the DNA from the nucleus of the cell, and put it into the egg cell. So effectively they are taking the genetic information from the animal, and putting it into an egg. Then they let that egg develop, and it goes through the normal stages of development: it divides into two cells, into four cells, into eight cells, into sixteen cells, and then forms into an embryo.

The nucleus is removed by punching a hole in the egg, then using a very small sucker to suck out the existing DNA. Then the opposite is done: the DNA is sucked out of the animal's cell and placed in the empty egg. This is done under a microscope in a laboratory, under sterile conditions, to avoid fungus and bacteria growing.

Different Types of Cloning
Embryo cloning is basically a medical technique which duplicates the process that nature uses to produce twins or triplets. One or more cells are removed from a fertilised embryo and encouraged to develop into one or more duplicate embryos. Twins or triplets are thus formed, with identical DNA. This has been done for many years on various species of animals, but only very limited experimentation has been done on humans.

Reproductive cloning involves producing a duplicate of an existing animal. It has been used to clone various mammals now, but the most famous cloned mammal is still "Dolly the Sheep". The DNA from an embryo is removed and replaced with the DNA from an adult animal. Then, the embryo is implanted in a womb and allowed to develop into a new animal. It has not been tried on humans.

Finally, therapeutic cloning is a procedure that starts off like adult DNA cloning. However, the stem cells (cells that can replicate indefinitely and which can differentiate into other cells) are removed from the embryo with the intent of producing tissue or a whole organ for transplant back into the person who supplied the DNA. The embryo dies in the process. The goal of therapeutic cloning is to produce a healthy copy of a sick person's tissue or organ for transplant in order to avoid organ transplants from other people. The tissue or organ would have the sick person's original DNA so there would be no fear of an immune reaction to the donor organ.

Why Clone?
Using these methods, there are many uses to which human cloning may be put to in the future ranging from life saving techniques that utilise cloned stem cells to create donor organs, to using manufactured bone, fat and connective tissue for cosmetic and reconstructive surgery, instead of using materials foreign to the body. There is also a great deal that we can learn about cells and the cell cycle from cloning, which could lead to breakthroughs such as learning how cells differentiate into specific kinds of tissue and how to switch cells on and off and thus be provided with a key to understanding and curing cancer.

The Arguments: Robin Lovell-Badge

Copyrighted imageCopyright: Used with permission
Dr Robin Lovell-Badge is head of research into developmental genetics at the National Institute of Medical Research. He is interested in how cells choose their fate and is familiar with the techniques used in cloning, having worked with embryonic stem cells from the mouse for about 25 years. He feels that research into cloning technology and maybe its application will be very useful in curing people with a wide range of diseases.

On cloning human beings:
"The issues that we are all concerned with are how to cure people of diseases, not make copies of people and I think that the technology is certainly not there, and there is no evidence that it's going to get there to be sufficiently successful to do reproductive cloning."

On the need to use an embryo on the way to creating new tissues from adult cells:
"I agree that using adult stem cells has potential, but we also don't know the limitations, so we mustn't get too excited yet about adult stem cells, because there are many potential problems.

There is a lot of evidence to suggest that cells actually know where they've come from, they have a memory where they are. So you're asking them not only to change their cell type, but to change where they come from. So we should do research on adult stem cells and embryonic stem cells.

I think that at the moment the practical barriers to reproductive cloning are so great; even though there are all these successes with animals, that the vast majority of attempts at reproductive cloning, fail somewhere in embryonic development. You could not possibly ask someone to accept the risk associated with failure of an embryo in the order of something like 90% or more. That's just too high.

I think the sorts of abnormalities that you get from cloning and in vitro fertilisation (IVF) are very species specific. In mice we can do IVF very successfully and never see any problems, but cloning is much more difficult, a lot of the embryos fail, and of those that are born, depending on which cell type you use as a donor, you can see a range of different problems in the cloned animals. So it's an unsafe technology, which certainly at the moment in my view shouldn't even be tried on humans, because you can't try it without risking it."

On whether problems that develop when cloning whole animals, will develop in cloned embryonic stem cells that scientists want to use to treat disease:
"It is certainly an issue we have to worry about, whether any embryonic stem cell line coming from a cloning attempt is normal, but you have to also look at the other side. Someone suffering from Parkinson’s disease might not mind that there's something not quite perfect about the cells you are putting back in there."

On the 14 day research limit on experimental research on human embryos:
"The 14 day limit is very sensible in many respects, it is the point before when the primitive nervous system begins to develop, and I think we're human because of our wonderful nervous systems. And 14 days is enough, because what we what to do is research in the dish, we don't want to research using surrogate mothers."

On the future:
"I think there will be a range of options available for curing people of disease and trauma and they will include therapies that have come from embryonic stem cells, whether by therapeutic cloning or otherwise, there will be use of adult stem cells, and there will be ways of reprogramming in situ if you like, making the stem cells that are present in the tissue to regenerate themselves, in a more efficient way than they normally do."

Copyrighted imageCopyright: Used with permission
Dr Michael Antoniou is a senior lecturer in the Division of Medical and Molecular Genetics at Guy’s, King’s & St Thomas’ School of Medicine in London. His area of expertise is chromatin domains, gene organisation and regulation of gene expression. The ultimate aim of his research is to design and deliver therapy gene units to adult stem cells that can address diseases such as muscular dystrophy.

On cloning human beings:
"There are certainly going to be people who will attempt it, whether they will be successful or not is another question. But the point is that the equipment and the know-how to try to clone, are actually readily available, and that is a worry.

I think even if we solved all of the technical problems, and we think that cloned humans are going to be normal; whatever that means, I think it is morally and ethically unacceptable to clone human beings. Therefore there should be an international ban on anything that will contribute to that, and most people that you talk to, agree in that regard."

On the need to use an embryo on the way to creating new tissues from adult cells:
"I think that what has been discovered, especially in the last couple of years, clearly shows that stem cells obtained from adults, have as much therapeutic potential as embryonic stem cells. In fact, it's such a new that we don't know the limits yet of adult stem cell potential. Because now we can take stem cells from the bone marrow, and we can not only regenerate the blood system, but potentially we can regenerate nervous tissue, muscle tissue, heart tissue, liver tissue. Really it's just growing all the time."

On whether problems that develop when cloning whole animals, will develop in cloned embryonic stem cells that scientists want to use to treat disease:
"There is published evidence from a very reputable group in the USA, that shows that actually even embryonic stem cells do have genetic instability, especially epigenetic instability."

On whether there is a need to use embryonic stem cells:
"We don't need to use embryonic stem cells because of what has been discovered in the last couple of years, which is that, adult stem cells are far more plentiful than originally thought and they can actually be isolated in large numbers, from a number of different tissues. Also, these cells can be grown in culture with varying degrees of efficiency, for example skin stem cells can be propagated for as long as a year. So although I agree that adult stem cell propagation is more difficult than embryonic stem cell modification, I think that it's clear that we can get enough to do the job, from a given person, and I think that's all that's important.

My feeling is that what's out there in the adult stem cells field is not being fully appreciated. Far more is going on than is being acknowledged. I do not understand why it's being said that embryonic stem cells offer the only hope.

I think that it's very important to study a genetic or a cellular phenomenon in its proper context, and I think that if you want to study the signals that trigger adult stem cells to go down a particular differentiation pathway, then you should study them in an adult context, and if you want to find out about embryonic signals, then you should study them in an embryonic context. But the other thing that seems to be remarkable about adult stem cells is their ability to adapt to the environment to which they are introduced, and then contribute to the repair of the area which has been damaged."

On the future:
"I think that it may not be necessary to use embryonic stem cells, because the way that things are progressing in the adult stem cell field, I feel that we will be able to get all we want from a person, at a time when we need it, and offer a range of regenerative stem cell-based therapies as a result."

The Arguments: Michael West

Copyrighted imageCopyright: Used with permission
Dr Michael West is president and chief executive officer of Advanced Cell Technology, Inc. (ACT), a biotechnology company based in the USA. ACT is a company engaged in the research and development of technologies enabling the genetic manipulation of cells to produce transgenic animals for pharmaceutical protein production. The company is also developing transgenic cloned cells and tissues for applications in cell and organ transplant therapy. Dr Michael West's research interests include age-related degenerative diseases, for example, Parkinson’s disease and arthritis.

On cloning human beings:
"What scientists were excited about when Dolly was cloned, what cloning means, is that you can take a skin cell back to an embryonic state and of course make a whole copy of you, and in that copy of you is liver, kidney and brain cells, all the cells of the human body, which means that we've found a way to take a skin cell and turn it into any other cell in the body. If we can do that with cells, not cloning people, but cells, it would be a revolution in medicine."

On the need to use an embryo on the way to creating new tissues from adult cells:
"We know that the embryonic stem cell can form every cell and tissue in the human body, but I would argue that we don't know that an adult stem cell can make every cell and tissue."

On cloning human embryos:
"We have cloned human embryos, not people. We're interested in cloning cells, not people. But I must say, because there's been so many stories written about this whole area of cloning, it’s cluttered with myth. And one of the important areas of myth, that we need to demythologise in thinking about human cloning, is that cloned animals are all abnormal. This results from scientists that mean well, but potentially have misinformed the public in their enthusiasm to say that we shouldn't clone a human being, because we don't know that we are safe. We have told the public that cloned animals have this and that problem, but in reality, in most cases, like in cattle cloning, the problems that we are seeing, are not related to cloning. The abnormalities relate to the procedure of having an embryo growing in the laboratory, not cloning itself, but the in vitro fertilisation (IVF) procedure.

As an example of cloned cattle, if you make an embryo of a cow in vitro, like we make IVF children, maybe 50% of those will successfully lead to a live birth. In the case of cloning, about 20% of mothers that have cloned embryos put in them will result in a healthy live birth in our hands. So the numbers aren't the same, but what I am saying is that the abnormalities you see are the same abnormalities as IVF. We have no reason to believe that cloning itself, at least in cattle, is introducing unique problems.

We don't know that a cloned human would be abnormal, but because we don't know that it wouldn't be, the scientific community is still saying we should not proceed with the cloning of a human being at this time.

In the case of the medical applications of cloning, we are talking about human lives at stake. We are talking about children with diabetes, people with Alzheimer’s disease and arthritis. In the case of reproductive cloning, maybe there's a childless couple, maybe the day would come when we as a society would allow reproductive cloning. So I would argue, let's agree that we don't do it now, but then let's put a timeframe on it, and say it won't happen for the next ten years, but we'll look at it again in ten years time."

On whether problems that develop when cloning whole animals, will develop in cloned embryonic stem cells that scientists want to use to treat disease:
"To the question, 'is it easier to clone cells than it would be to clone a person?', the answer I think I can comfortably say is: it's far easier. We have nearly 70% certainty that we'll get a cloned embryo and potentially we could get stem cells, in the case of a human, whereas the actual cloned animal is far more difficult to get. So even though animal cloning isn't that efficient today, you would expect that the production of embryos from stem cells would be far easier to do."

On whether there is a need to use embryonic stem cells:
"As scientists we are enthusiastic about our own research, that's what makes science work, but we have to think about the patients first, and I think we should ratchet back a step on our enthusiasm and say 'we should do all of these things'.

We don't know which is going to be best for specific diseases or particular individuals. We just don't know. We can't predict. There's no point in stopping research in one area to concentrate on another. It is ethically unacceptable not to do the research.

A well-known ethicist says 'what's the rush' because of these ethical discussions, let's just wait a few years and see how these adult stem cells do. My point is, some people don't have a 10 years. For some people, that's a lifetime and I think that it's immoral and insensitive, not to allow all researchers to work as quickly as they can, to cure these life-threatening diseases."

On the 14 day research limit on experimental research on human embryos:
"I believe that 14 day limit is an important one, because what we are saying is, we're proposing making primitive cells, not a pregnancy. If you allow these cells, these embryonic cells and these pre-implantation embryos, past 14 days, something changes. It's called individualisation, you'd cross a line in development when those primitive cells, where there is no body cells of any kind, start to form a human being. And to say that we would create a human being, even in its earliest stages of development, and then harvest tissues from them, is a completely different argument and I, for one, am not comfortable with that."

On the future:
"I think that in the future there will never need to be the day when a patient with an incurable degenerative disease, where some cells and tissues are sick and need to be replaced, that the patients will need to die. I think that we'll have what we call regenerative medicine - the ability of making new young cells and tissues to replace diseased ones."

Further Reading

Clone: The Road to Dolly and the Path Ahead
Gina Kolata (William Morrow and Company, 1997)

Remaking Eden: Cloning and Beyond in a Brave New World
Lee M. Silver (Avon Books, 1997)

Department of Health Report on Human Cloning (1998)
This report is the Government response to the report by the Human Genetics Advisory Commission and the Human Fertilisation and Embryology Authority on cloning issues in reproduction, science and medicine Department of Health.

Cloning for medicine
I. Wilmut ( Scientific American, 279, pp 58-63, 1998)
A personal account of the cloning of Dolly and an exploration of some of the possible applications.

About the authors

Robin Lovell-Badge is Head of Stem Cell Biology and Developmental Genetics at the National Institute for Medical Research. He is Honorary Professor at University College London's Department of Anatomy and Developmental Biology and President of the Institute of Animal Technology, as well as serving on advisory committees.

Dr Michael Antoniou is Reader in Molecular Genetics at Kings College, London. His research centres on chromatin domains, gene organisation and regulation of gene expression with the aim of designing and delivering therapy gene units to adult stem cells to inheritable diseases.

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